Abstract

BACKGROUND: Aldosterone has a rapid, non-genomic, inhibitory effect on macroscopic basolateral K+
conductance in the human colon, reducing its capacity for Cl− secretion. The molecular identity of the
K+ channels constituting this aldosterone inhibitable K+ conductance is unclear.

AIM: To characterise the K+ channel inhibited by aldosterone present in the basolateral membrane of
human colonic crypt cells.

METHODS: Crypts were isolated from biopsies of healthy sigmoid colon obtained during colonoscopy.
The effect of aldosterone on basolateral K+ channels, and the possible involvement of Na+:H+ exchange,
were studied by patch clamp techniques. Total RNA from isolated crypts was subjected to reverse
transcriptase-polymerase chain reaction (RT-PCR) using primers specific to intermediate conductance
K+ channels (KCNN4) previously identified in other human tissues.

RESULTS: In cell attached patches, 1 nmol/l aldosterone significantly decreased the activity of intermediate
conductance (27 pS) K+ channels by 31%, 53%, and 54% after 1, 5 and 10, minutes, respectively.
Increasing aldosterone concentration to 10 nmol/l produced a further 56% decrease in channel
activity after five minutes. Aldosterone 1–10 nmol/l had no effect on channel activity in the presence of
20 µmol/l ethylisopropylamiloride, an inhibitor of Na+:H+ exchange. RT-PCR identified KCNN4
mRNA, which is likely to encode the 27 pS K+ channel inhibited by aldosterone.

CONCLUSION: Intermediate conductance K+ channels (KCNN4) present in the basolateral membranes of
human colonic crypt cells are a target for the non-genomic inhibitory effect of aldosterone, which
involves stimulation of Na+:H+ exchange, thereby reducing the capacity of the colon for Cl− secretion.